Toward a Universal Readout for ¹⁸F-Labeled Amyloid Tracers: The CAPTAINs Study

Area of Science:

• Nuclear Medicine
• Neurology
• Radiochemistry

Background:

• Three 18F-labeled PET tracers are approved for assessing cerebral amyloid plaque pathology in suspected Alzheimer disease (AD).
• Existing visual rating protocols approved by regulatory agencies differ across these tracers, despite similar scanning procedures.

Purpose of the Study:

• To evaluate the comparability of three approved visual rating protocols for amyloid PET tracers.
• To assess the performance of these protocols when applied by experts and nonexperts in classifying scans as amyloid-positive or -negative.

Main Methods:

• An international multicenter study involved expert and nonexpert raters evaluating scans from 18F-florbetaben, 18F-florbetapir, and 18F-flutemetamol.
• Scans were rated using all three approved visual rating protocols in a randomized order, with raters blinded to the tracer used.
• Metrics analyzed included visual reader agreement, interrater reliability, and agreement with quantitative measures, stratified by rater expertise.

Main Results:

• Experts showed no significant differences in agreement metrics across the visual rating protocols, indicating robustness.
• Nominal differences favored the 18F-florbetaben protocol for higher interrater reliability and accuracy, particularly under low confidence.
• Nonexpert raters exhibited significant protocol-dependent differences, with moderate-to-fair accuracy and the 18F-florbetapir protocol showing the highest reliability.

Conclusions:

• High interrater agreement was observed across all 18F-labeled amyloid tracers, irrespective of the visual rating protocol used, especially among experts.
• Visual interpretation of amyloid PET imaging appears to be highly standardizable and independent of the specific protocol for experienced readers.
• Developing a universal visual assessment protocol for all amyloid imaging tracers is feasible and could significantly aid less experienced readers.